Objective Patients with oral squamous cell carcinoma (OSCC) may choose best supportive care (BSC) as initial treatment over active treatment for several reasons. However, no previous reports have compared the clinical characteristics of OSCC patients opting for BSC as initial treatment with those receiving standard treatment. This study retrospectively analyzed these differences to identify the factors influencing this decision. Materials and methods This retrospective study was conducted at Niigata University Medical and Dental Hospital, using medical records within January 2018-December 2022 (follow-up until June 2023). Among 135 patients with primary OSCC, received BSC (BSC group) and underwent standard treatment according to the disease stage (non-BSC group). Data included demographic and tumor characteristics, Eastern Cooperative Oncology Group Performance Status (ECOG-PS), underlying diseases, neutrophil-lymphocyte ratio (NLR), albumin levels, living situation (with family, in a care facility, or alone), rationale for BSC selection (untreatable due to poor general condition or no desire for treatment), overall survival (OS) rate, and disease-specific survival (DSS) rate. Age, NLR, and albumin levels were assessed using Student's t-test. Stage classification, ECOG-PS, and living situation were analyzed using the chi-square test. OS and DDS were calculated using the Kaplan-Meier method and compared using the log-rank test. Multiple logistic regression analysis identified factors associated with BSC. Results  The BSC group included 11 males and 13 females (mean age: 84 years; range: 47-92). The non-BSC group included 67 males and 44 females (mean age: 67.4 years; range: 31-89). Female predominance was higher in the BSC group (male-female ratio: 1:1.2) than in the non-BSC group (1:0.7). Primary sites were the lower gingiva in the BSC and the tongue in the non-BSC group. The BSC group exhibited higher NLR (p=0.50) and a significantly lower albumin level (p<0.001). Stage classification (I/II vs. III/IV) and ECOG-PS (0-1 vs. 2-4) differed significantly between groups (p<0.001). Cardiovascular disease was the most frequent comorbidity in both groups. Living situation exhibited no significant differences (p=0.99). The cumulative one-year OS rate in the BSC group was 29.8%, compared to 97.2% and 81.5% in the non-BSC group at one and five years, respectively. The cumulative one-year DSS rate in the BSC group was 31.9%, and 97.2% and 82.8% at one and five years in the non-BSC group were p<0.001 for OS and DSS. Age (OR: 1.20, 95% CI: 1.10-1.36; p=0.0008), stage classification (I/II vs. III/IV) (OR: 13.79, 95% CI: 2.34-137.75; p=0.0026), psychiatric disorder (OR: 8.73, 95% CI: 2.34-137.75; p=0.021), albumin level (OR: 0.03, 95% CI: 0.002-0.24; p=0.003) were factors in BSC. Among patients aged ≥75 years, stage classification (I/II vs. III/IV) (OR: 19.08, 95% CI: 2.51-321.07; p=0.0027), albumin level (OR: 0.003, 95% CI: 9.0×10-0.098; p=0.01) remained significant predictors of BSC. Conclusion Patients opting for BSC tended to be older. Stage classification and albumin level were key factors in BSC across all patients, including those aged ≥75 years. Early diagnosis and timely intervention are vital to improve treatment opportunities. Collaborative discussions among patients, families, and healthcare providers are crucial to develop individualized care plans, ensuring that patients receiving BSC can approach end-of-life care with dignity.